Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle

Abstract

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are essential for ovarian follicular growth in sheep, whereas only GDF9 is essential in mice suggesting that the roles of these oocyte-derived growth factors differ among species. At present, however, there is only limited information on the action of BMP15 and GDF9 in other species. Thus, the aim of this experiment was to determine the effect of neutralizing GDF9 and/or BMP15 in vivo on ovarian follicular development and ovulation rate in cattle through active immunization using the mature regions of the proteins or peptides from the N-terminal area of mature regions. Immunization with the BMP15 peptide, with or without GDF9 peptide, significantly altered (increased or decreased) ovulation rate. In some animals, there were no functional corpora lutea (CL), whereas in others up to four CL were observed. From morphometric examination of the ovaries, immunization with GDF9 and/or BMP15 reduced the level of ovarian follicular development as assessed by a reduced proportion of the ovarian section occupied by antral follicles. In addition, immunization against GDF9 and/or BMP15 peptides reduced follicular size to !25% of that in the controls. In conclusion, immunization against GDF9 and BMP15, alone or together, altered follicular development and ovulation rate in cattle. Thus, as has been observed in sheep, both GDF9 and BMP15 appear to be key regulators of normal follicular development and ovulation rate in cattle.

Effects of immunization against bone morphogenetic protein-15 and growth differentiation factor-9 on ovarian function in mares

“…Four mares in this group had only one or no ovulations, whereas mares with several ovulations had a relatively greater incidence of abnormally small follicles from which there were ovulations. This is similar to reports by Juengel et al (2009) where it was reported that some vaccinated cattle failed to have ovulations, while the animals with multiple ovulations appeared to have ovulations from smaller than average follicles. In deer immunized against BMP15, ovulation rate (as indicated by fawns/doe born) was increased over three breeding seasons even though animals had a significant immune response.…”

“…Additionally, altered ovarian activity and decreased ovulation rates suggest that antibodies created in response to immunization were effective in binding and inactivating the BMP-15 protein in mares. Results of the present study for BMP-15 treatment are similar to those reported in other BMP-15 immunization studies in sheep and cattle, with an overall decrease in ovulations and some animals having a complete cessation of ovulations (Juengel, 2002;Juengel et al, 2009Juengel et al, , 2004McNatty et al, 2007). Four mares in this group had only one or no ovulations, whereas mares with several ovulations had a relatively greater incidence of abnormally small follicles from which there were ovulations.…”

“…Mutations affecting expression of either the BMP-15 or GDF-9 gene induce sterility in homozygous mutant sheep, while heterozygotes have increased fertility rates, indicating that altered gene expression for these growth factors have a dramatic impact on fertility (Galloway et al, 2000;Hanrahan et al, 2004). These studies have been replicated through immunization against BMP-15 and GDF-9 in sheep, deer, and cattle and have produced varying results, with some treatments increasing fertility and others inducing sterility (Juengel, 2002;Juengel et al, 2009;Eckery et al, 2014;). The present study, therefore, is aimed to determine effects of immunization against BMP-15 and GDF-9 on ovarian function in the mare.…”

Study on the relationship between expression patterns of cocaine-and amphetamine regulated transcript and hormones secretion in porcine ovarian follicles

“…Despite such limitations, our results indicates that the concentrations of E 2 and P in follicular fluid of large, medium and small follicles had no significant difference, which suggests that CART has no direct regulatory effect on the production of these two hormones in porcine antral follicles. Follicular growth and development are regulated by endocrine factors [40,41], including E 2 and P, which are important indicators to reflect the state of follicular growth. Smith et al [12] demonstrated that CART had an inhibitory effect on in vitro production of E 2 by granulosa cells.…”

Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles

“…In sheep and cattle, immunization against GDF-9 and BMP-15, alone or together, showed that GDF-9 and BMP-15 were associated with corpus luteum activity Juengel et al 2009). Similar to the report from Silva et al (2005) that GDF-9 was observed in goat corpus lutea, we found that both GDF-9 and BMP-15 presented in corpus lutea of adult human.…”